Alanines, reaction with carbonyl

The acid moiety of an amino acid can be activated for acyl substitution rather than converted to an aldehyde for acyl addition. Boc-alanine was converted to an acyl imidazole by reaction with carbonyl diimidazole (CDI see chapter two, section 2.4), and then condensed with the magnesium enolate of the mono ethyl ester of malonic acid to give keto-ester 5.9. Subsequent catalytic hydrogenation of the ketone moiety gave ethyl 3-hydroxy-5-(N-Boc amino)penlanoate, 5.10 Once the o... 

When carbonyl compounds are used as electrophiles reaction with 4-monosub-stituted-5(4//)-oxazolones affords substituted serines after subsequent hydrolytic ring opening of the initial aldol product. As an example, 4-methyl-2-phenyl-5(4//)-oxazolone 193, prepared from alanine, reacts with benzaldehyde in a base-catalyzed addition to give, after hydrolysis, a 3 1 mixture of threo- and... 

The hetero-Diels-Alder reaction of activated butadienes with carbonyl compounds is a convenient method for the preparation of precursors of sugars. Up to three chiral centers are created simultaneously. The high-pressure [4 + 2]cycloaddition of l-methoxybuta-1,3-diene 32 to N-mono- and N,N-diprotected alaninals was investigated [42-45]. The Eu(fod)3-mediated reaction of 32 with alaninal 25 gave a mixture of four diastereoisomers, which was then subjected to acidic isomerization, leading to the thermodynamically more stable pair of adducts syn-33 and anti-34, with predominance of the latter isomer (Scheme 12). The N-monoprotected alaninals reacted with a moderate ryn-diastereoselectivity. This method was used in the synthesis of purpurosamines (see Sec. DI.C). 

Reduction of ethyl 2 -ketopantothenate to ethyl 2 -d-pantothenate ((g) in Fig. 8). The rate of condensation of ketopantolactone or D-pantolactone with ethyl (3-alanine, yielding ethyl 2 -ketopantothenate (0 in Fig. 8) or ethyl D-panto-thenate, respectively, is quite fast compared to the condensation of ketopantolactone or D-pantolactone with (3-alanine, and the reaction with ethyl (3-alanine proceeds more stoichiometrically [117]. Since the enzymatic hydrolysis of ethyl D-pantothenate has been established [118], if the stereoselective reduction of ethyl 2 -ketopantothenate to ethyl D-pantothenate is possible, both the troublesome resolution and the incomplete condensation might be avoided at the same time. Carbonyl reductase of C. macedoniensis is used for this purpose. Washed cells of the yeast converted ethyl 2 -ketopantothenate (80 g/1) almost specifically to ethyl D-pantothenate (> 98% e.e.), with a molar yield of 97.2% [103]. In a similar manner, 2 -ketopantothenonitrile (50 g/1) was converted to D-pan-tothenonitrile (93.6% e.e.), with a molar yield of 95.6%, on incubation with Sporidiobolus salmonicolor cells as a catalyst [104],... 

A-Phthaloyl-protected (S)-phenylalanine has been used as a ligand for rhodium in the formation of metallocarbenes from diazo compounds for C-H insertion reactions (Section D.1.2.2.3.2.). Ar-Sulfonyl-protected (S)-alanine and (S)-valine are efficient ligands for chiral Lewis acids used in the Diels-Alder reaction (Section D.1.6.1.1.1.3.). A -Sulfonyl-pro-tected (S)-phenylalanine methyl ester has been used for the enantioselective protonation of lactone enolates (Section D.2.I.). The terf-butyl ester of (S)-valine readily forms imines with carbonyl compounds which are used for the highly efficient alkylations of their azaenolates (Sections D.1.1.1.4.1D.1.5.2.4.). All these derivatives can be obtained by the standard methods described in Houben-Weyl3. 

Thus, if the amino acid (Figure 8.23) is alanine (R3 = -CH3), widely represented in must and wine, the corresponding aldehyde is ethanal. If the amino acid is methionine (R4 = CH3-S-CH2-CH2-), which is certainly only present in small quantities but is reputed to be highly reactive with carbonylated compounds, then methional, or -methyl-S-propanal, is produced. This compound is thermally unstable and evolves rapidly, via a Retro-Michael reaction, into acrolein and methanethiol (Figure 8.28). These smell of cooked cauliflower, wet dog, etc. In wine, part of the methional returns to methionol via catalyzed reduction by alcohol dehydrogenase with NADH. 

Chemical inhibition of L-phenylalanine ammonia lyase activity may be achieved by the use of typical carbonyl reagents such as sodium borohydride and potassium cyanide. Treatment of the enzyme with tritiated sodium borohydride and subsequent hydrolysis gave alanine in which the majority of the radioactivity was confined to the jj-methyl group . Similarly reaction with potassium cyanide and hydrolysis gave aspartic acid labelled exclusively in the -carboxyl group . These observations led to the proposal that the active site of the enzyme, like that of the related L-histidine ammonia lyase , contains a dehydro-alanine residue... 

FIGURE 7.10 Formation of the succinimido ester of IV-succinimidoxycarbonyl-P-alanine by reaction of three molecules of IV-hydroxysuccinimide (HONSu) with one molecule of dicy-clohexylcarbodiimide.25 The first molecule (N1) reacts to form the O-succinimido-isourea. The second molecule (N2) ruptures the ring by attack at the carbonyl, generating a nitrene that rearranges to the esterified carboxyalkyl isocyanate. The third molecule (N3) attacks the carbonyl of the latter. R3 = R4 = cyclohexyl SuN- = succinimido. 

In this section we refer to types of addition to the carbonyl group, which by their very nature lead to C4-elongation. Examples are found in the addition of furan derivatives and [4+2] cycloaddition. We have recently described [39] the stereoselective addition of 2-furyl-lithium 26 to N,N-diprotected alaninals. For example, the reaction of 26 with alaninal 25 led to a mixture of diastereoisomers syn-21 and anti-28, with predominance of the latter isomer (Scheme 10). A similar method was used in the synthesis of methyl a-D-lincosaminide (see Sec. III.F). 

The aza-Michael reaction yields, complementary to the Mannich reaction, P-amino carbonyl compounds. If acrylates are applied as Michael acceptors, P-alanine derivatives such as 64 and 65 are obtained. The aza-Michael reaction can be catalyzed by Bronsted acids or different metal ions. Good results are also obtained with FeCl3, as shown in Scheme 8.29. The addition of HNEt2 to ethyl acrylate (41f), for example, requires 10mol% of the catalyst and a reaction time of almost 2 days [94], The addition of piperidine to a-amino acrylate 41g is much faster and yields a,P-diaminocarboxylic acid derivative 65 [95]. 

K. Oyama, K. Kihara, and Y. Nonaka, On the mechanism of the action of thermolysin kinetic study of the thermolysin-catalyzed condensation reaction of N-benzyloxy-carbonyl-t-aspartic add with L-phenyl-alanine methyl ester, J. Chem. Soc. Perkin Trans. 2 1981a, 356-360. 

ESR Spectral Data on Free Radicals and Browning in the Reaction of Sugars and Other Carbonyl Compounds with a- or B-Alanine ... 

Pyruvic acid is an important metabolite in its own right as we shall see shordy. It is the simplest a-keto-acid (2-oxopropanoic acid). Having the two carbonyl groups adjacent makes them more reactive the ketone is more electrophilic and enolizes more readily and the acid is stronger. Pyruvate is in equilibrium with the amino acid alanine by an aminotransferase reaction catalysed by pyridoxal (above). 

Another important asymmetric epoxidation of a conjugated systems is the reaction of alkenes with polyleucine, DBU and urea H2O2, giving an epoxy-carbonyl compound with good enantioselectivity. The hydroperoxide anion epoxidation of conjugated carbonyl compounds with a polyamino acid, such as poly-L-alanine or poly-L-leucine is known as the Julia—Colonna epoxidation Epoxidation of conjugated ketones to give nonracemic epoxy-ketones was done with aq. NaOCl and a Cinchona alkaloid derivative as catalyst. A triphasic phase-transfer catalysis protocol has also been developed. p-Peptides have been used as catalysts in this reaction. ... 

---